96 articles - From Saturday Mar 26 2022 to Friday Apr 01 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
| Am J Hematol |
First Versus Second Generation Bruton Tyrosine Kinase Inhibitors in Waldenström's Macroglobulinemia: A Systematic Review and Meta-analysis. Grade 3/4 atrial fibrillation was higher in 1st generation BTKi (3.1% vs 0.4%), however, grade 3/4 infections and neutropenia were more frequent in 2nd BTKi (20.9% vs 13.2%, 17.7% vs 12%, respectively). The efficacy of 1st and 2nd generation BTKis is comparable. The 1st generation BTKi were associated with a higher risk of atrial fibrillation whereas infections and neutropenia occurred more frequently in 2nd generation BTKi. |
| Haematologica |
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
Integration of multiparameter flow cytometry score improves prognostic stratification provided by standard models in primary myelofibrosis. As regards IPSS, C-indexes were 0.67 and 0.74 for standard and MFC-enhanced model, respectively (Z score |
Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Following the Discontinuation of Tyrosine Kinase Inhibitors. By multivariate analysis, only the duration of MR 4 or MR 4.5 =5 |
| Ann Oncol |
333HLA class II Immunogenic Mutation Burden Predicts Response to Immune Checkpoint Blockade. HLA class II IMM burden identified patients with NSCLC and melanoma that attained longer survival after ICB treatment. Our findings suggest that HLA class II IMMs may impact responses to ICB in a manner that is distinct and complementary to HLA class I-mediated responses. |
Adjuvant Abemaciclib Combined with Endocrine Therapy for High Risk Early Breast Cancer: Safety and Patient-Reported Outcomes From the monarchE Study. In patients with high risk EBC, adjuvant abemaciclib+ET has an acceptable safety profile and tolerability is supported by PRO findings. Most AEs were reversible and manageable with comedications and/or dose modifications, consistent with the known abemaciclib toxicity profile. |
Phase 2 single arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi Sarcoma (cKS). This prospectively designed phase II study of nivolumab and ipilimumab demonstrates promising activity of this combination in progressive cKS representing a new treatment option in this population. |
| Blood |
A study of Ruxolitinib-response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis. Our study provides clinical evidence for ruxolitinib as a front-line agent for pediatric HLH. The efficacy was particularly exemplified with stratified regiment based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform ( as ChiCTR2000031702. |
Activation of the Zinc-sensing receptor GPR39 promotes T cell reconstitution after hematopoietic cell transplant in mice. Accumulated Zn in thymocytes during development was released into the extracellular milieu after HSCT conditioning, where it triggered regeneration by stimulating endothelial cell-production of BMP4 via the cell surface receptor GPR39. Dietary supplementation of Zn was sufficient to promote thymic function in a mouse model of allogeneic HSCT, including enhancing the number of recent thymic emigrants in circulation; although direct targeting of GPR39 with a small molecule agonist enhanced thymic function without the need for prior Zn accumulation in thymocytes. Together, these findings not only define an important pathway underlying tissue regeneration, but also offer an innovative preclinical approach to treat lymphopenia in HSCT recipients. |
Both G protein-coupled and immunoreceptor tyrosine-based activation motif receptors mediate venous thrombosis in mice. Thrombin generation and clot formation were normal in blood from high dose DAPT- or ibrutinib-treated mice; however, platelet adhesion and platelet-neutrophil aggregate formation at the vein wall were reduced in high dose DAPT- or ibrutinib-treated mice. In summary, VT initiation requires platelet activation via GPCRs and ITAM receptors. Strong inhibition of either signaling pathway reduces VT in mice. |
Efficacy and safety of CD19-specific CAR T-cell-based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. The duration of remission in CNSL was longer than that in BM disease. CD19 CAR T-cell therapy may provide a potential treatment option for those previously excluded CNSL patients with manageable neurotoxicity. Clinical trials were registered at as # NCT02782351 and as # ChiCTR-OPN-16008526. |
Extracellular vesicles and PDL1 suppress macrophages inducing therapy resistance in TP53-deficient B-cell malignancies. Disruption of EV bound PD-L1 by anti-PD-L1 antibodies or PD-L1 CRISPR-KO improved macrophage phagocytic capacity and in vivo therapy response. Thus, we demonstrate enhanced EV-release and increased PD-L1 expression in TP53-deficient B-cell lymphomas as novel mechanisms of macrophage function alteration in CIT resistance. This study indicates the use of checkpoint inhibition in the combination treatment of B-cell malignancies with TP53 loss. |
Functional mapping of PHF6 complexes in chromatin remodeling, replication dynamics and DNA repair. Moreover, following DNA damage, PHF6 localizes to sites of DNA injury and its loss impairs the resolution of DNA breaks with consequent accumulation of single- and double-stranded DNA lesions. Native chromatin immunoprecipitation sequencing analyses reveal that PHF6 specifically associates with difficult to replicate heterochromatin at satellite DNA regions enriched in Histone H3 lysine 9 trimethyl marks (H3K9me3) and single molecule locus-specific analyses identify PHF6 as an important regulator of genomic stability at fragile sites. These results extend our understanding of the molecular mechanisms controlling HSC homeostasis and leukemia transformation by placing PHF6 at the crossroads of chromatin remodeling, replicative fork dynamics and DNA repair. |
Hematopoietic stem cell transplantation for adolescents and adults with inborn errors of immunity, an EBMT IEWP study. On multivariable analysis EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT. |
Macrophage NOX2 NADPH oxidase maintains alveolar homeostasis in mice. Moreover, deletion of NOX2 preferentially in macrophages was sufficient for mice to develop an activated CD11bhigh AM subset and accompanying pro-inflammatory sequela. Additionally, we showed that the altered resident macrophage transcriptional profile in the absence of NOX2 is tissue-specific as these changes were not seen in resident peritoneal macrophages. Thus, these data demonstrate that absence of NOX2 in alveolar macrophages leads to their pro-inflammatory remodeling and dysregulates alveolar homeostasis. |
Pegcetacoplan for Paroxysmal Nocturnal Hemoglobinuria. Pegcetacoplan inhibits complement proximally at the level of C3 and is highly effective in treating persistent anemia resulting from C3-mediated extravascular hemolysis. We describe the rationale for C3 inhibition in the treatment of PNH and discuss preclinical and clinical studies using pegcetacoplan and other compstatin derivatives. We propose an approach for sequencing complement inhibitors in PNH. |
Studies in a mosaic DBA patient and chimeric mice reveal erythroid cell-extrinsic contributions to erythropoiesis. In contrast, mice transplanted with Flvcr1-deleted (unable to export heme) and wildtype marrow cells at ratios of 50:50 or 80:20 have normal numbers of red cells. Additional studies suggest that heme exported from DBA erythroid cells might impede the nurse cell function of central macrophages of erythroblastic islands to impair the maturation of genetically-normal co-adherent erythroid cells. These findings have implications for the gene therapy of DBA and may provide insights into why del(5q) myelodysplastic syndrome patients are anemic despite being mosaic for chromosome 5q deletion and loss of RPS14. |
| Blood Adv |
A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia. In a validation cohort of 99 VITT patients identified by clinic-pathological adjudication, procoagulant flow cytometry identified 93% of VITT cases including ELISA-negative and SRA-negative patients. The in vitro effect of IVIg and fondaparinux trended with the clinical response seen in patients. Induction of Fc |
Anti-CD19 CAR T Cells in Combination with Ibrutinib for the Treatment of Chronic Lymphocytic Leukemia. In CLL patients not achieving a CR despite at least 6 months of ibrutinib, adding huCART-19 mediated a high rate of deep and durable remissions. ClinicalTrials. gov number, NCT02640209. |
Effect of Additional Cytogenetic Abnormalities on Survival in Arsenic Trioxide-Treated Acute Promyelocytic Leukemia. We performed a pooled analysis of exclusively ATO-treated patients at a single academic institution and from the ALLG APML4 and Alliance C9710 studies to determine the prognostic importance of additional cytogenetic abnormalities and/or complex karyotype. We demonstrate inferior event-free survival for patients harboring complex karyotype [hazard ratio (HR): 3.74, 95% confidence interval: 1.63-8.56, P = 0.002] but not for patients harboring additional cytogenetic abnormalities (HR 2.13, 95% CI: 0.78-5.82, P = 0.142). These data support the role for full karyotypic analysis for al patients with APL and indicate a need for novel treatment strategies to overcome this adverse effect for APL harboring complex karyotype. |
Malaria-associated adhesion molecule activation facilitates the destruction of uninfected red blood cells. Moreover, we observed that a soluble parasite derived factor promotes the adhesive phenotype of uRBCs, as the incubation of RBCs with filtered malaria conditioned media reproduced the same adhesive effect in malaria culture derived uRBCs. Eventually, Lu/BCAM and CD44 activation facilitates the adherence to extracellular-matrix components of the red pulp resulting in the enhanced splenic retention of uRBCs. Thus, our results suggest a novel adhesion molecule dependent mechanism augmenting malaria induced anemia. |
Megakaryocyte/platelet-derived TGF-ß1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver. In BM cell culture, TPO treatment increased the number of megakaryocytes from WT-mice by ~3-fold, which increased a further ~2-fold in the presence of a TGF-ß1-neutralizing antibody, and increased the number of megakaryocytes from PF4Cre;Tgfb1flox/flox mice ~5-fold. Our data reveal a new role for TGF-ß1 produced by megakaryocyte/platelets in regulating its own production in BM via increasing TPO production in the liver. Further studies are required to determine the mechanism. |
Safety and efficacy of atezolizumab with obinutuzumab and bendamustine in previously untreated follicular lymphoma. The efficacy of atezo-G-bendamustine in previously untreated FL did not appear superior to G-bendamustine efficacy as seen in the GALLIUM trial, and the addition of atezo to G-bendamustine was associated with an increased risk of AEs. Particularly due to the unfavorable safety profile, this regimen cannot be recommended in patients with previously untreated FL. This trial is registered at as NCT02596971. |
SIRPa+ macrophages are increased in patients with FL who progress or relapse after frontline lenalidomide and rituximab. Three macrophage populations were significantly increased in tissue samples collected at progression compared with prior to frontline treatment: CD68+CD115+ (p=0.02), CD68+CD115+CD172a+ (p=0.02) and CD68+CD163+CD172a+ (p= 0.01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. Therapies targeting specific macrophage populations may yield novel approaches for improving outcomes with frontline R2. |
Src-related thrombocytopenia: a fine line between a megakaryocyte dysfunction and an immune-mediated disease. In summary, in addition to causing impaired platelet production, SRC-RT may associate immune dysregulation, and increased platelet consumption. In families in whom several members are responsive to ITP directed therapies, an underlying Src p. E527K variant should be excluded. |
The Immune Microenvironment Shapes Transcriptional and Genetic Heterogeneity in Chronic Lymphocytic Leukemia. Clonal trajectories are shaped by the LN milieu where T-cell immunity may contribute to suppress clonal outgrowth. The clinical study is registered at clinicaltrials. gov as NCT00923507. |
| Haematologica |
Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes, risk factors and genotypes. Findings were validated in an Australian independent cohort of children with ALL (n=797) where two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1 464 (9.2%) patients experienced CNS toxicity with cumulative incidence of 8.7% (95% CI: 7.31-10.20) at 12 months from diagnosis. Patients aged =10 years had higher risk of CNS toxicity than younger patients (16.3% vs 7.4%; p. |
Fc galactosylation of anti-platelet hIgG1 alloantibodies enhance complement activation on platelets. Elevated Fc galactosylation and to a lesser extent sialylation significantly increased the complement activating properties of anti- HLA and anti-HPA-1a mAbs. We propose that both the breadth of the polyclonal immune response, with recognition of different HLA epitopes and in some cases HPA antigens and the type of Fc glycosylation, can provide an optimal stoichiometry for C1q binding and subsequent complement activation. These factors can shift the effect of a platelet alloimmune response to a clinically relevant response, leading to complement mediated clearance of donor platelets as observed in PR. |
Final analysis of the phase 3 non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs 34.5%, respectively) and shorter administration time (3-5 minutes vs 3-7 hours) supporting DARA SC as a preferable therapeutic choice. ClinicalTrials. gov Identifier: NCT03277105. |
Glycolytic enzyme PFKFB3 determines bone marrow endothelial progenitor cell damage post chemotherapy and irradiation. Clinically, PFKFB3-induced FOXO3A expression and NF- |
Preclinical evaluation and structural optimization of anti-BCMA CAR to target multiple myeloma. Nonetheless, critical differences were observed in off-target activation, exhaustion, and activation markers expression and in vivo antitumoral activity mediated by these different constructs. Interestingly, we noted that CD8-based hinge, combined with a 4-1BB intracellular domain, proved superior compared to IgG4 connecting regions, and/or a CD28 signaling moiety respectively. Overall, this study emphasizes the influence of CAR primary structure on its function and led to the identification of a highly efficient BCMA-specific CAR, namely H8BB, which displayed superior anti-tumor activity both in vitro and long-term in vivo efficacy. |
TAL1 cooperates with PI3K/AKT pathway activation in T-cell acute lymphoblastic leukemia. As a consequence, we find that TAL1+AKTE17K transformed cells are more sensitive to PI3K-AKT pathway inhibition compared to AKTE17K transformed cells, related to the negative effect of TAL1 in the absence of activated PI3K-AKT signaling. We also find that both TAL1 and PI3K-AKT signaling increase the DNA-repair signature in T cells resulting in synergy between PARP and PI3KAKT pathway inhibition. In conclusion, we have developed a novel mouse model for TAL1+AKTE17K driven T-ALL development and identify a vulnerability of these leukemia cells to PI3K-AKT and PARP inhibitors. |
| J Hematol Oncol |
Immune cell atlas of cholangiocarcinomas reveals distinct tumor microenvironments and associated prognoses. This study suggests that the densities of Granzyme-B + CD8 + effector T cells and non-exhausted PD-1 - EOMES - CD8 + T cells and the PD-L1 status in the tumor-associated macrophages are prognostic makers in cholangiocarcinomas. The study also supports targeting PD-L1 + tumor-associated macrophages as the immunotherapy for cholangiocarcinoma. |
| Lancet Haematol |
Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial. Standard of care plus four doses of rituximab did not significantly improve event-free survival over standard of care. Rituximab is beneficial in acute lymphoblastic leukaemia but four doses during induction is likely to be insufficient. Cancer Research UK and Blood Cancer UK. |
In-vivo T-cell depleted reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation for patients with acute lymphoblastic leukaemia in first remission: results from the prospective, single-arm evaluation of the UKALL14 trial. FMA reduced-intensity conditioned allogeneic HSCT in older patients with acute lymphoblastic leukaemia in first complete remission provided good disease control with moderate GVHD, resulting in better-than-expected event-free survival and overall survival in this high-risk population. Strategies to reduce infection-related TRM will further improve outcomes. Cancer Research UK. |
Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study. The use of mass spectrometry also highlighted the potential hidden clinical significance of MGIP. Our study suggests the association of monoclonal gammopathies with a variety of clinical phenotypes and decreased overall survival. Funding Stand Up To Cancer Dream Team, the Multiple Myeloma Research Foundation, and National Institutes of Health. |
Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study. We observed high response rates to contemporary therapies that were of short duration. These data identify unmet needs among patients with follicular lymphoma, especially those who are refractory to alkylating agents, and might provide evidence by which clinical trials evaluating novel treatments could be assessed. Genentech and the National Cancer Institute. |
| Leukemia |
Autologous or allogeneic hematopoietic cell transplantation for relapsed or refractory PTCL-NOS or AITL. In the multivariable analysis, alloHCT tended to be associated with better progression-free survival (PFS) in REL (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.53-1.03), and significantly better PFS in PIF (HR 0.64; 95% CI: 0.46-0.88) compared with autoHCT. The subgroup analysis with propensity-score matching showed that alloHCT was associated with better OS for REL-sensitive and PIF-nonremission disease. This study suggested that the advantage of alloHCT for R/R PTCL-NOS or AITL is different, depending on the disease status at HCT. |
LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Altogether, 107 deaths occurred, due to progressive disease (n |
RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia. From repurposing drug screens in RAS-activated AML cells, we identified pyrvinium pamoate, an anti-helminthic agent efficiently inhibiting the growth of RAS+ |
RNAseqCNV: analysis of large-scale copy number variations from RNA-seq data. RNAseqCNV outperforms alternative RNA-seq based algorithms in calling CNVs in the ALL dataset, especially in samples with a high proportion of CNVs. The CNV calls were highly concordant with DNA-based CNV results and more reliable than conventional cytogenetic-based karyotypes. RNAseqCNV provides a method to robustly identify copy number alterations in the absence of DNA-based analyses, further enhancing the utility of RNA-seq to classify ALL subtype. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
Alternative RNA Splicing Defects in Pediatric Cancers: New Insights in Tumorigenesis and Potential Therapeutic Vulnerabilities. Alternative splicing plays a critical role in the formation and growth of pediatric cancers, and our institutional cohort confirms and highlights the broad spectrum of affected genes in a variety of cancers. Further studies that elucidate the mechanisms of disease-inducing splicing events will contribute toward the development of novel therapeutics. |
| Blood |
| Blood Cancer J |
Induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma: an update. In fact, the updated 2021 European Haematology Association (EHA) and European Society for Medical Oncology (ESMO) clinical practice guidelines recommend the use of either lenalidomide-Vd (VRd), or daratumumab-thalidomide-Vd (Dara-VTd) as first-line options for transplant-eligible NDMM patients, and when not available, thalidomide-Vd (VTd) or cyclophosphamide-Vd (VCd) as acceptable alternatives. Quadruplet regimens featuring anti-CD38 monoclonal antibodies are extremely promising and remain heavily investigated, as is the incorporation of more recent proteasome inhibitors such as carfilzomib. This review will focus on induction therapies prior to ASCT examining the latest data and guidelines on triplet and quadruplet regimens. |
| J Hematol Oncol |
Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells. Among cell exhaustion characteristics, impaired mitochondrial function and dynamics are considered hallmarks. Here, we review the mitochondrial characteristics of exhausted T cells and particularly discuss different aspects of mitochondrial metabolism and plasticity. Furthermore, we propose a novel strategy of rewiring mitochondrial metabolism to emancipate T cells from exhaustion and of targeting mitochondrial plasticity to boost CAR-T cell therapy efficacy. |
Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy. This review summarizes recent work on the regulation of ECM stiffness in cancer, the effects of ECM stiffness on tumor progression, cancer immunity and drug resistance. We also discuss the potential targets that may be druggable to intervene ECM stiffness and tumor progression. Based on these advances, future efforts can be made to develop more effective and safe drugs to interrupt ECM stiffness-induced oncogenic signaling, cancer progression and drug resistance. |
Targeting the histone H3 lysine 79 methyltransferase DOT1L in MLL-rearranged leukemias. Recent advances in the development of small molecule degraders, including heterobifunctional degraders and molecular glues, provide valuable insights and references for DOT1L degraders. However, drug R&D strategies and platforms need to be developed and preclinical experiments need to be performed with the purpose of blocking DOT1L-associated PPIs. DOT1L epigenetic-based combination therapy is worth considering and exploring, but the therapy should be based on a thorough understanding of the regulatory mechanism of DOT1L epigenetic modifications. |
| Lancet Haematol |
Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations. The expert panel recommended that patients with polycythaemia vera who are younger than 60 years and have not had previous thrombotic events should start cytoreductive drug therapy if at least one of the following criteria are fulfilled: strictly defined intolerance to phlebotomy, symptomatic progressive splenomegaly, persistent leukocytosis (>15 |
| Leukemia |
Myeloid neoplasms and clonal hematopoiesis from the RUNX1 perspective. Accumulating pieces of evidence also indicate the leukemogenic role of wild-type RUNX1 in certain situations. Based on these efforts, part of the molecular mechanisms of disease development as a consequence of dysregulated RUNX1-regulatory networks have become increasingly evident. This review highlights the recent advances in the field of RUNX1 research and discusses the critical roles of RUNX1 in hematopoiesis and the pathobiological function of its alterations in the context of disease, particularly myeloid neoplasms, and clonal hematopoiesis. |
Questions concerning tyrosine kinase-inhibitor therapy and transplants in chronic phase chronic myeloid leukaemia. However, in those who candidates are physicians and patients need to weigh benefits and risks of TKI-therapy versus a transplant. We suggest transplants should be more often considered in the metric when counseling people with chronic phase CML unlikely to achieve TFR with TKI-therapy. We question whether we are discounting a possible important therapy intervention; we think so. |
Letters to the editors and authors’ replies
| Am J Hematol |
| Blood Cancer J |
| J Hematol Oncol |
Metabolic characteristics and prognostic differentiation of aggressive lymphoma using one-month post-CAR-T FDG PET/CT. Higher SUVMax at one month post-CAR-T is associated with higher risk of PD and death. SUVMax |
| Lancet Haematol |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
| Leukemia |